Pathways of arsenic uptake and detoxification (NIH Grant R37 GM55425)
The overall goal of research in the Rosen laboratory is a detailed molecular analysis of the arsenic transporters and modifying enzymes.Arsenic, a Group 1 human carcinogen, ranks first on the EPA's Superfund list. Arsenic enters the human body from both geological and anthropogenic sources. Because of the ubiquity of arsenic in the environment, every organism has developed transport systems for the efflux and detoxification of arsenic. Chronic exposure to arsenic has been linked to cardiovascular and peripheral vascular diseases, neurological disorders, diabetes and various cancers. Arsenic-containing drugs are used as chemotherapeutic agents for the treatment of leukemia and parasitic diseases. An understanding of both arsenic chemistry and the molecular details of arsenic transport systems is essential for alleviating the problems of arsenic toxicity, as well as for the rational design of drugs to treat drug-resistant microbes and cancer cells.
Selected recent publications (from more than 260 articles, chapters and books):
- Zhu YG, Xue XM, Kappler A, Rosen BP, Meharg AA. Linking Genes to Microbial Biogeochemical Cycling: Lessons from Arsenic. Environ Sci Technol. in press (2017
- Hao, X., Li, X., Pal, C., Hobman, J., Larsson, D.G., Saquib, Q., Alwathnani, H.A., Rosen, B.P., Zhu, Y.G., Rensing, C. Bacterial resistance to arsenic protects against protist killing. Biometals. 30,307-311 (2017). PMID: 28210928
- Chen, J., Li, J., Jiang, X. and Rosen B.P. Conserved cysteine residues determine substrate specificity in a novel As(III) S-adenosylmethionine methyltransferase from Aspergillus fumigatus. Mol Microbiol. 104, 250-259 (2017). PCMID: PMC5380552
- Chen, J. and Rosen, B.P. Organoarsenical biotransformations by Shewanella putrefaciens. Environ Sci Technol. 50,7956-7963(2016). PCMID: PCM27366920
- Yang, H.C. and Rosen, B.P. New mechanisms of bacterial arsenic resistance. Biomed. J. 39,5-13(2016). PMID 27105594
- Huang, K., Chen, C., Zhang. J., Tang, Z., Shen, Q., Rosen, B.P. and Zhao, F.J. Efficient arsenic methylation and volatilization mediated by a novel bacterium from an arsenic-contaminated paddy soil. Sci. Technol. 50, 6389-6396(2016). PCMID: PCM27258163
- Li, J., Mandal, G. and Rosen, B.P. Expression of arsenic resistance genes in the obligate anaerobe Bacteroides vulgatus ATCC 8482, a gut microbiome bacterium. Anaerobes, 39,117-123(2016). PCMID: PMC4984537
- Chen, J., Yoshinaga, M., Garbinski, L. and Rosen, B.P. Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance. Molec. Microbiol. 100,945-953 (2016). Accompanied by microcommentary. PCMID: PMC4992400
- Nadar, V.S., Yoshinaga, M., Pawitwar, S., Kandavelu, P., Sankaran, B. and Rosen, B.P. Structure of the ArsI C-As lyase: insights into the mechanism of degradation of organoarsenical herbicides and growth promoters. Molec. Biol. 428, 2462–2473 (2016). PCMID: PCM27107642
- Tang, Z., Lv, Y., Chen, F., Zhang,W., Rosen, B.P. and Zhao, F.G. Arsenic methylation in Arabidopsis thaliana expressing an algal arsenite methyltransferase gene increases arsenic phytotoxicity. J. Agric. Food Chem. 64, 2674–2681. PMCID: PMC4984539
- Duan, G. Hu, Y., McDermott, J., Chen, J., Schneider, S., Saur, N. Rosen, B.P., Liu, Z. and Zhu, Y.G. Inositol permeases AtINT2 and AtINT4 transport arsenic into Arabidopsis thaliana Nature Plants, 21,15202(2016). Carried by many international news feeds. PMCID: PMC4758254
- Kumar, N.V., Yang. J., Pillai, J.K., Rawat, S., Solano, C. Kumar, A., Grøtli, M., Stemmler, T.L., Rosen, B.P., Tamás, M.J. Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8, Cell. Biol. 36, 913-922 (2015). PCMID: PMC4810476
- Dong, H., Madegowda. M., Nefzi, A., Houghten, R.A., Giulianotti, M.A. and Rosen, B.P. Identification of small molecule inhibitors of human As(III) S-adenosylmethionine methyltransferase (AS3MT). Chem. Res. Toxicol. 21, 2419-2425 (2015). Editors’ Choice Paper.
Books and Chapters
- Walmsley, A.R. and Rosen, B.P. Efflux mechanisms in drug resistance. In Antimicrobial Drug Resistance, Douglas L. Mayers, editor, Humana Press, in press (2008).
- Rensing, C. and Rosen, B.P. Heavy metal cycles. In Encyclopedia of Microbiology, Third Edition, Moselio Schaechter, Editor-in-Chief, Elsevier, in press (2008).
- Rosen, B.P. and Liu, Z. Transport pathways for arsenic and selenium. Environmental International., Sunbaek Bang, Editor. Transport pathways for arsenic and selenium: A minireview in press (2008).
- Liu, Z. and Rosen, B.P. Uptake pathways for arsenic and selenium. Proceedings of the XIIIth Annual Meeting of All India Congress of Cytology and Genetics, A. Giri, Editor, in press (2008).
- Bhattacharjee, H., Mukhopadhyay, R. and Rosen, B.P. Aquaglyceroporins: ancient channels for metalloids. J. Biol. 7, 33 (2008).
- Bhattacharjee, H., Rosen, B.P. and Mukhopadhyay, R., Metalloid transport by aquaglyceroporins.In Handbook of Experimental Pharmacology, Eric Beitz, Editor, 190, 309-325(2009).
- Rosen, B.P. and Tamás, M.J. Arsenic transport in prokaryotes and eukaryotic microbes, in MIPs (major intrinsic proteins) and their role in the exchange of metalloids, Thomas Jahn and Gerd Patrick Bienert, editors, Landes Bioscience Publishers, In press (2009).